DE1545844C - 3 Amino benzisothiazoles and processes for their preparation - Google Patents

Description

It has been found that 3-Amino-benzisothiazoles of the general formula I

R, -

in which R _{1 represents} a / 9-chloroethyl radical, an alkyl radical with 1 to 4 carbon atoms, a benzyl radical and a phenyl or cyclohexyl radical optionally substituted by a methyl group and R _{2 represents} a hydrogen atom or a nitro group, and their salts with strong acids superior to l- (p-chlorobenzyl) 2-methylbenzimidazole in the antifungal effect on some fungi. These compounds are obtained if 3-halobenzisothiazolium halides of the general formula!

II

T X

in which X stands for a chlorine or bromine atom and R ₁ and R _{2 have} the abovementioned meaning, are reacted with ammonia at temperatures between 0 and 10 ^° C. and the compounds obtained are optionally converted into their salts with strong acids.

For performing this method is 1 mole of N-substituted 3-HaIogen-benzisothiazoliumhalogenid at 5 to 10 ⁰ C in excess ammonia, preferably in a methanolic NH ₃ solution (11 5 Mol NH ;,) added.

The N-substituted ones used as starting material 3-Halogen-benzisothiazolium halides, preferably 3-chloro-benzisothiazolium chlorides, are made from N-substituted dithiosalicylic acid amides and phosphorus pentahalides.

The new 3-amino-benzisothiazoles are colorless, crystalline compounds. They are weak bases and as such form salts only with strong acids.

They show excellent in vitro inhibition values in Trichophyton mentagrophytes, Candida albicans, Penicillium commune, Aspergillus niger and Mikrosporium felineum. Some compounds also show a clear effect on experimental guinea pig trichophytosis when administered orally.
. The new compounds are intended to be used as antimycotics in human and veterinary medicine and as pesticides.

example 1
3-methylamino-benzisothiazole · HCl

1io g (0.5 mol) of 2-methyl-3-chloro-benzisothiazoliumchlorid (finely powdered) to be at 5 quickly with vigorous stirring in 500 ml to 10 ⁰ C a saturated _{Mcthanol-Nll: i} -I.ösung (2.5 mol ) entered. To complete the reaction, the mixture is stirred for a further 5 minutes, then the precipitated ammonium chloride is filtered off with suction and the filtrate is evaporated in vacuo. The syrup obtained is taken up in 150 ml of hydrochloric acid 1: 1 (0.75 mol). The initially clear solution solidifies into a solid paste after a few minutes. After standing in the ice bath for a while (30 minutes), the hydrochloride which has crystallized out is filtered off with suction, washed with a little cold water and dried. This gives 55 g (55 ° / ₀ of theory) of 3-methyl-amino-benzisothiazol · HCl. The compound crystallized from ethanol as colorless prisms, melting point 220 ⁰ C (Subl.). ,,

; The compounds listed below will be. prepared in the same ^manner:

3-ethyl-amino-benzisothiazole · HCl

After recrystallization from ethanol, the substance yields colorless, well-defined, leafy prisms with a melting point of 171 ° C (sub.).

3-propyl-ariiino-benzisothiazole · HCl

Colorless prisms made of methanol with a melting point of 111 ° C.

3-butyl-amino-benzisothiazole · HCl

The compound crystallizes from acetonitrile in colorless, coarse prisms at 155 to 157 ° C melt, then crystallize again and show a second melting point at 212 ° C.

3-isobutyl-amino-benzisothiazole · HCl

After recrystallization from methanol, the substance is obtained in large, colorless platelets. which melt at 187 ° C, then crystallize again and have a second melting point at 216 ° C show.

3 - [/? - chloroethyl] -amino-benzisothiazole · HCl

Colorless, coarse, well-defined prisms (methanol) with a melting point of 152 ° C.

3-Cyclohexyl-amino-benzisothiazole · HCl

Solid prisms, colorless from ethanol, with a melting point of 166 ° C.

3- [4-Methyl-cyclohexyI] -amino-benzisothiazole · HCl Colorless after recrystallization from ethoxyethanol Crystals with a melting point of 160 ° C.

3- [3-Methyl-cyclohexyl] -amino-benzisothiazole · HCl From ethanol, colorless needles with a melting point 197 ° C.

3- [2-Methyl-cyclohexyl] -amino-benzisothiazole · HCl

Recrystallized from dimethyl sulfoxide, the compound gives colorless prisms with a melting point of 210 ^° C.

3-benzyl-amino-benzisothiazole

The substance was isolated as the free base. The compound forms colorless, tough prisms (methanol) with a melting point of 85 ° C.

3-phenylamino-ben / isothiazole

The compound was isolated as the free base. Colorless, bulbous crystals (ethanol) from Melting point 99 "C.

3- [4-methyl-phenyl] -amino-benzisothiazole

The free base crystallizes from ethanol in long, yellowish needles with a melting point of 144 ° C.

Claims (2)

Claims: 1. Compounds of the general formula R ₂ I. NH-R ₁ wherein R _{1 represents} a β-chloroethyl radical, an alkyl radical with 1 to 4 carbon atoms, a benzyl radical and a phenyl or cyclohexyl radical optionally substituted by a methyl group and R _{2 represents} a hydrogen atom or a nitro group, and their salts with strong acids. 2. Process for the preparation of N-substituted 3-aminobenzisothiazoles, characterized in that that one 3-halobenzisothiazolium halides of the general formula R ₁ X ¹⁹ in which X stands for a chlorine and bromine atom and R ₁ and R _{2 have} the meaning given in claim 1, are reacted with ammonia at temperatures between 0 and 10 ⁰ C and the compounds thus obtained are optionally converted into their salts with strong acids.